Variant rs1052165 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001384361.1(PMEL):c.741C>T(p.Pro247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,526 control chromosomes in the GnomAD database, including 64,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4213 hom., cov: 31)

Exomes 𝑓: 0.28 ( 60295 hom. )

Consequence

PMEL
NM_001384361.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

PMEL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=3.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMEL	NM_001384361.1 linkuse as main transcript	c.741C>T	p.Pro247=	synonymous_variant	6/11	ENST00000548747.6	NP_001371290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMEL	ENST00000548747.6 linkuse as main transcript	c.741C>T	p.Pro247=	synonymous_variant	6/11	1	NM_001384361.1	ENSP00000448828	P4	P40967-1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31905

AN:

151668

Hom.:

4217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.259

AC:

65187

AN:

251430

Hom.:

9375

AF XY:

0.274

AC XY:

37272

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0503

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.282

AC:

411719

AN:

1461740

Hom.:

60295

Cov.:

AF XY:

0.287

AC XY:

208491

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.210

AC:

31882

AN:

151786

Hom.:

4213

Cov.:

AF XY:

0.209

AC XY:

15515

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.0559

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.269

Hom.:

10238

Bravo

AF:

0.197

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

EpiCase

AF:

0.285

EpiControl

AF:

0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.3

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over